Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia

Proceedings of the National Academy of Sciences of the United States of America - Tập 95 Số 6 - Trang 3117-3121 - 1998
Katherine Conant1, Alfredo Garzino-Demo1, Avindra Nath1, Justin C. McArthur1, William Halliday1, Christopher Power1, Robert C. Gallo1, Eugene O. Major1
1Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, Building 36, Room 5W21, National Institutes of Health, Bethesda, MD 20892; Institute of Human Virology, University of Maryland, Baltimore, MD 21201; Departments of Internal Medicine (Section of Neurology) and Medical Microbiology and Pathology, University of Manitoba, MB, Canada R3E 0W3; and Department of Neurology, Johns Hopkins University School of Medicine, and Department of Epidemiology,...

Tóm tắt

Activated monocytes release a number of substances, including inflammatory cytokines and eicosanoids, that are highly toxic to cells of the central nervous system. Because monocytic infiltration of the central nervous system closely correlates with HIV-1-associated dementia, it has been suggested that monocyte-derived toxins mediate nervous system damage. In the present study, we show that the HIV-1 transactivator protein Tat significantly increases astrocytic expression and release of monocyte chemoattractant protein-1 (MCP-1). Astrocytic release of β-chemokines, which are relatively less selective for monocytes, including RANTES, macrophage inflammatory protein-1α, and macrophage inflammatory protein-1β, was not observed. We also show that MCP-1 is expressed in the brains of patients with HIV-1-associated dementia and that, of the β-chemokines tested, only MCP-1 could be detected in the cerebrospinal fluid of patients with this condition. Together, these data provide a potential link between the presence of HIV-1 in the brain and the monocytic infiltration that may substantially contribute to dementia.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 95 Số 6

3117-3121

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